Reversal of Adynamic Bone Disease By Lowering of Dialysate Calcium

A Haris; D J Sherrard; G Hercz

Disclosures

Kidney Int. 2006;70(5):931-937. 

In This Article

Abstract and Introduction

Abstract

Adynamic bone disease (ABD) is increasingly recognized, especially in dialysis patients treated with oral calcium carbonate, vitamin D supplements, or supraphysiological dialysate calcium. We undertook this study to assess the effect of lowering dialysate calcium on episodes of hypercalcemia, serum parathyroid hormone (PTH) levels as well as bone turnover. Fifty-one patients treated with peritoneal dialysis and biopsy-proven ABD were randomized to treatment with control calcium, 1.62 mM, or low calcium, 1.0 mM, dialysate calcium over a 16-month period. In the low dialysate calcium group, 14 patients completed the study. This group experienced a decrease in serum total and ionized calcium levels, and an 89% reduction in episodes of hypercalcemia, resulting in a 300% increase in serum PTH values, from 6.0±1.6 to 24.9±3.6 pM (P<0.0001). Bone formation rates, all initially suppressed, at 18.1±5.6 µm2/mm2/day rose to 159±59.4 µm2/mm2/day (P<0.05), into the normal range (>108 µm2/mm2/day). In the control group, nine patients completed the study. Their PTH levels did not increase significantly, from 7.3±1.6 to 9.4±1.5 pM and bone formation rates did not change significantly either, from 13.3±7.1 to 40.9±11.9 µm2/mm2/day. Lowering of peritoneal dialysate calcium reduced serum calcium levels and hypercalcemic episodes, which resulted in increased PTH levels and normalization of bone turnover in patients with ABD.

Introduction

Renal osteodystrophy, one of the major complications of end-stage renal disease (ESRD), although recognized decades ago and studied extensively since then, continues to be a challenging problem for nephrologists. In the 1970s and early 1980s, management of hyperphosphatemia, the hyperparathyroid state, and bone aluminum deposition was the major concern.[1] Over the past 15 years, the spectrum of renal osteodystrophy has changed, and adynamic bone disease (ABD) has been increasingly recognized. ABD is characterized by reduced synthesis of bone matrix owing to decreased osteoblastic and osteoclastic activity.[2] In association with reduced bone formation rates (BFR), there is a lack of osteoid accumulation differentiating this abnormality from osteomalacia. According to the Toronto Renal Osteodystrophy Study, in the 1990s the most prevalent form of bone disease was the non-aluminum-related ABD, occurring in 34% of 256 ESRD patients who underwent bone biopsy.[2,3,4] In a retrospective analysis of 1429 iliac crest biopsies performed in Italy between 1985 and 1994, 15.3% showed non-aluminum-related adynamic bone histology. Its frequency was fairly constant during the observational period, whereas the prevalence of aluminum bone disease gradually decreased, from 36 to 4%.[5] In another European study, 42% of 81 ESRD patients had biopsy-proven ABD, with a greater frequency noted in peritoneal than in hemodialysis (HD)-treated patients.[6] A similar result was shown by Sánchez et al.,[7] who found a 63.2% frequency of low turnover bone disease in 57 patients treated with peritoneal dialysis. Interestingly, 32% of patients with advanced renal failure, before initiation of renal replacement therapy, had ABD, in spite of avoiding any vitamin D therapy.[8]

One of the unresolved issues is whether ABD is a disease or just an asymptomatic condition. Theoretically, low BFR predisposes patients to the risk of poor healing of microfractures and increased fracture incidence.[9,10] Also, as the calcium (Ca)-buffering effect of bone is diminished, patients on Ca-containing phosphate binders and high dialysate Ca may have frequent episodes of hypercalcemia.[1] In addition, these episodes of hypercalcemia may result in Ca deposition in the vasculature and myocardium, shortening life expectancy in the ESRD population.[11]

The serum Ca level is one of the major determinants of parathyroid hormone (PTH) secretion. In continuous ambulatory peritoneal dialysis (CAPD) patients, the continuous positive Ca balance resulting from the elevated dialysate Ca may result in suppressed PTH levels. Consequently, the present study was undertaken to investigate the role of suppressed PTH levels in the development of low turnover bone disease. The aim was to assess whether lowering of dialysate Ca is able to enhance PTH secretion, increase BFR, and improve bone histology in patients treated with peritoneal dialysis and biopsy-proven ABD.

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